Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Jan 1;183(1):195–201. doi: 10.1084/jem.183.1.195

Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model

PMCID: PMC2192412  PMID: 8551223

Abstract

Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.

Full Text

The Full Text of this article is available as a PDF (3.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azzawi M., Bradley B., Jeffery P. K., Frew A. J., Wardlaw A. J., Knowles G., Assoufi B., Collins J. V., Durham S., Kay A. B. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. doi: 10.1164/ajrccm/142.6_Pt_1.1407. [DOI] [PubMed] [Google Scholar]
  2. Beasley R., Roche W. R., Roberts J. A., Holgate S. T. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989 Mar;139(3):806–817. doi: 10.1164/ajrccm/139.3.806. [DOI] [PubMed] [Google Scholar]
  3. Bochner B. S., Undem B. J., Lichtenstein L. M. Immunological aspects of allergic asthma. Annu Rev Immunol. 1994;12:295–335. doi: 10.1146/annurev.iy.12.040194.001455. [DOI] [PubMed] [Google Scholar]
  4. Broide D. H., Gleich G. J., Cuomo A. J., Coburn D. A., Federman E. C., Schwartz L. B., Wasserman S. I. Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway. J Allergy Clin Immunol. 1991 Oct;88(4):637–648. doi: 10.1016/0091-6749(91)90158-k. [DOI] [PubMed] [Google Scholar]
  5. Brusselle G. G., Kips J. C., Tavernier J. H., van der Heyden J. G., Cuvelier C. A., Pauwels R. A., Bluethmann H. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy. 1994 Jan;24(1):73–80. doi: 10.1111/j.1365-2222.1994.tb00920.x. [DOI] [PubMed] [Google Scholar]
  6. Campbell H. D., Tucker W. Q., Hort Y., Martinson M. E., Mayo G., Clutterbuck E. J., Sanderson C. J., Young I. G. Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci U S A. 1987 Oct;84(19):6629–6633. doi: 10.1073/pnas.84.19.6629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  8. Dahinden C. A., Geiser T., Brunner T., von Tscharner V., Caput D., Ferrara P., Minty A., Baggiolini M. Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine. J Exp Med. 1994 Feb 1;179(2):751–756. doi: 10.1084/jem.179.2.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Monchy J. G., Kauffman H. F., Venge P., Koëter G. H., Jansen H. M., Sluiter H. J., De Vries K. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am Rev Respir Dis. 1985 Mar;131(3):373–376. doi: 10.1164/arrd.1985.131.3.373. [DOI] [PubMed] [Google Scholar]
  10. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. Am Rev Respir Dis. 1990 Oct;142(4):863–871. doi: 10.1164/ajrccm/142.4.863. [DOI] [PubMed] [Google Scholar]
  11. Dubucquoi S., Desreumaux P., Janin A., Klein O., Goldman M., Tavernier J., Capron A., Capron M. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med. 1994 Feb 1;179(2):703–708. doi: 10.1084/jem.179.2.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gleich G. J., Flavahan N. A., Fujisawa T., Vanhoutte P. M. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol. 1988 May;81(5 Pt 1):776–781. doi: 10.1016/0091-6749(88)90931-1. [DOI] [PubMed] [Google Scholar]
  13. Hamid Q., Azzawi M., Ying S., Moqbel R., Wardlaw A. J., Corrigan C. J., Bradley B., Durham S. R., Collins J. V., Jeffery P. K. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991 May;87(5):1541–1546. doi: 10.1172/JCI115166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ishida K., Thomson R. J., Beattie L. L., Wiggs B., Schellenberg R. R. Inhibition of antigen-induced airway hyperresponsiveness, but not acute hypoxia nor airway eosinophilia, by an antagonist of platelet-activating factor. J Immunol. 1990 May 15;144(10):3907–3911. [PubMed] [Google Scholar]
  15. Iwama T., Nagai H., Tsuruoka N., Koda A. Effect of murine recombinant interleukin-5 on bronchial reactivity in guinea-pigs. Clin Exp Allergy. 1993 Jan;23(1):32–38. doi: 10.1111/j.1365-2222.1993.tb02481.x. [DOI] [PubMed] [Google Scholar]
  16. Jose P. J., Griffiths-Johnson D. A., Collins P. D., Walsh D. T., Moqbel R., Totty N. F., Truong O., Hsuan J. J., Williams T. J. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994 Mar 1;179(3):881–887. doi: 10.1084/jem.179.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kurup V. P., Choi H., Murali P. S., Coffman R. L. IgE and eosinophil regulation in a murine model of allergic aspergillosis. J Leukoc Biol. 1994 Nov;56(5):593–598. doi: 10.1002/jlb.56.5.593. [DOI] [PubMed] [Google Scholar]
  18. Lopez A. F., Sanderson C. J., Gamble J. R., Campbell H. D., Young I. G., Vadas M. A. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988 Jan 1;167(1):219–224. doi: 10.1084/jem.167.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mauser P. J., Pitman A., Witt A., Fernandez X., Zurcher J., Kung T., Jones H., Watnick A. S., Egan R. W., Kreutner W. Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma. Am Rev Respir Dis. 1993 Dec;148(6 Pt 1):1623–1627. doi: 10.1164/ajrccm/148.6_Pt_1.1623. [DOI] [PubMed] [Google Scholar]
  20. Ohashi Y., Motojima S., Fukuda T., Makino S. Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. Am Rev Respir Dis. 1992 Jun;145(6):1469–1476. doi: 10.1164/ajrccm/145.6.1469. [DOI] [PubMed] [Google Scholar]
  21. Ramsay A. J., Husband A. J., Ramshaw I. A., Bao S., Matthaei K. I., Koehler G., Kopf M. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994 Apr 22;264(5158):561–563. doi: 10.1126/science.8160012. [DOI] [PubMed] [Google Scholar]
  22. Ramsay A. J., Kohonen-Corish M. Interleukin-5 expressed by a recombinant virus vector enhances specific mucosal IgA responses in vivo. Eur J Immunol. 1993 Dec;23(12):3141–3145. doi: 10.1002/eji.1830231215. [DOI] [PubMed] [Google Scholar]
  23. Resnick M. B., Weller P. F. Mechanisms of eosinophil recruitment. Am J Respir Cell Mol Biol. 1993 Apr;8(4):349–355. doi: 10.1165/ajrcmb/8.4.349. [DOI] [PubMed] [Google Scholar]
  24. Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
  25. Rot A., Krieger M., Brunner T., Bischoff S. C., Schall T. J., Dahinden C. A. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992 Dec 1;176(6):1489–1495. doi: 10.1084/jem.176.6.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sibille Y., Reynolds H. Y. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev Respir Dis. 1990 Feb;141(2):471–501. doi: 10.1164/ajrccm/141.2.471. [DOI] [PubMed] [Google Scholar]
  27. Walker C., Bode E., Boer L., Hansel T. T., Blaser K., Virchow J. C., Jr Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis. 1992 Jul;146(1):109–115. doi: 10.1164/ajrccm/146.1.109. [DOI] [PubMed] [Google Scholar]
  28. Walker C., Kaegi M. K., Braun P., Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991 Dec;88(6):935–942. doi: 10.1016/0091-6749(91)90251-i. [DOI] [PubMed] [Google Scholar]
  29. Walker C., Virchow J. C., Jr, Bruijnzeel P. L., Blaser K. T cell subsets and their soluble products regulate eosinophilia in allergic and nonallergic asthma. J Immunol. 1991 Mar 15;146(6):1829–1835. [PubMed] [Google Scholar]
  30. Wardlaw A. J., Dunnette S., Gleich G. J., Collins J. V., Kay A. B. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Relationship to bronchial hyperreactivity. Am Rev Respir Dis. 1988 Jan;137(1):62–69. doi: 10.1164/ajrccm/137.1.62. [DOI] [PubMed] [Google Scholar]
  31. Weller P. F. Eosinophils: structure and functions. Curr Opin Immunol. 1994 Feb;6(1):85–90. doi: 10.1016/0952-7915(94)90038-8. [DOI] [PubMed] [Google Scholar]
  32. Yamaguchi Y., Hayashi Y., Sugama Y., Miura Y., Kasahara T., Kitamura S., Torisu M., Mita S., Tominaga A., Takatsu K. Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J Exp Med. 1988 May 1;167(5):1737–1742. doi: 10.1084/jem.167.5.1737. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES